TECHNICAL FIELD
[0001] The present invention generally relates to a method of measuring the concentration
of a nonelectrolyte in a solution in which one or more electrolytes and one or more
nonelectrolytes coexist. Further, the present invention relates to a preparation method
and a preparation apparatus capable of preparing a mixed solution containing one or
more nonelectrolytes of a given concentration by measuring the concentration of said
nonelectrolytes in an electrolyte solution. The present invention is used particularly
in the food industry and the pharmaceutical industry and, in particular, effectively
used for the measurement of the concentration of a dialysing solution (dialysate)
and the preparation thereof in the medical care field.
BACKGROUND ART
[0002] Conventionally, an electrolyte such as salt or sodium carbonate and a nonelectrolyte
such as sugar or alcohol are often added to and mixed with a polar solvent such as
water or the like in the food industry and the pharmaceutical industry. Further, in
the medical care field, a water solution in which sodium chloride as an electrolyte,
glucose as a nonelectrolyte and other small amounts of components are dissolved is
utilized as a dialysate used for a dialysing treatment.
[0003] When these products are manufactured, since it is difficult to directly measure the
concentration of nonelectrolytes in the solution, the electrolytes and the nonelectrolytes
in the solution have conventionally been set to given concentrations, respectively
by adding predetermined amounts of electrolytes and nonelectrolytes to a predetermined
amount of water or a polar solvent which is calculated to have a given concentration.
[0004] However, in this method, because the electrolytes and the like absorb water and change
weight while they are stored and further weighing errors are caused by the vibration
of a balance and the like, even if the predetermined amounts of electrolytes and nonelectrolytes
are weighed, the concentration of a resulting solution is not accurately made to a
given concentration. In additon, each time a necessary amount of the solution is changed,
necessary amounts of electrolytes, nonelectrolytes, water and the like must be recalculated.
[0005] Further, for example, as to the dialysate, medicines used in the preparation of the
dialysis solution have conventionally been divided into a so-called agent A mainly
composed of sodium chloride and a so-called agent B composed of sodium hydrogencarbonate
and they have been supplied to medical sites as undiluted solutions of given concentrations
in a liquid state. Therefore, in the medical sites, the dilution ratios for the thus
supplied undiluted solutions of agent A and agent B were calculated based on the respective
concentrations and the dialysate was prepared by stirring and mixing predetermined
amounts of the respective undiluted solutions with a predetermined amount of diluting
water in a preparation tank.
[0006] Recently, however, there is a proposal in which the agent A and agent B used in the
preparation of the dialysate are supplied in a powder state to medical institutions,
and the dialysate having a given concentration is prepared at the medical sites by
dissolving these powdered medicines in water, respectively, to make a liquid agent
A and a liquid agent B each having a given concentration and thereafter mixing these
liquid agents A and B.
[0007] Various methods are available to measure the concentration of electrolytes such as
sodium haydrogencarbonate used as agent B, and in particular, an electric conductivity
meter is widely used because it has many advantages such as a simple construction,
easy handling and high reliability resulting from a lower number of factors by which
a mesured value is infleneced.
[0008] Therefore, in the preparation of the dialysate, the concentration of a water solution
containing the agent B composed of sodium hydrogencarbonate can be simply measured
using the electric conductivity meter or the like. On the other hand, the agent A
mainly composed of sodium chloride contains grape sugar (glucose) as a nonelectrolyte
in additon to sodium chloride, potassium chloride, calcium chloride, magnesium chloride,
sodium acetate etc. as electrolytes. It has conventionally been thought impossible
to measure the concentration of the glucose in a water solution containing the agent
A using an electric conductivity meter.
[0009] That is, the electric conductivity meter is not applicable to nonelectrolytes which
are not dissociated to generate ions because the electric conductivity meter uses
an electric current flowing through a solution due to the ions generated by the dissociation
of substances dissolved in a polar solvent such as water.
[0010] Although refractometers, polarimeters and the like are as instruments for directly
measuring the concentration of nonelectrolytes in a solution, these instruments are
disadvantageous in that they are complex in construction, difficult to handle, have
low reliability and measured values are liable to vary depending upon how samples
are prepared.
[0011] Therefore, concerning the agent A of a dialysate, as described above, predetermined
amounts of sodium chloride (electrolyte) etc. and glucose (nonelectrolyte) determined
by calculation are added to a predetermined amount of water calculated to have a given
concentration, thereby the electrolytes and the nonelectrolyte in the water solution
are set to given concentrations, respectively.
[0012] Consequently, there arises the same problems as the above in the preparation of the
dialysing solution, that is, because the amount of the liquid is increased by the
dissolution of the nonelectrolyte, the electrolytes such as sodium chloride etc. and
glucose or the like absorb water to change their weight while being stored, as well
as weighing errors caused by the vibration of the balance, even if predetermined amounts
of electrolytes and glucose are weighed, the concentration of the resulting solution
is not accurately set to a given concentration. Furthermore, each time a necessary
amount of a solution is changed, necessary amounts of electrolytes, nonelectrolyte,
water and the like must be recalculated.
DISCLOSURE OF INVENTION
[0013] Taking the above circumstances into consideration, an object of the present invention
is to provide a method of directly and accurately measuring the concentration of a
nonelectrolyte in a solution which contains electrolytes and nonelectrolytes by using
a simple instrument.
[0014] Another object of the present invention is to provide a preparation method and a
preparation apparatus capable of simply and accurately preparing a mixed solution
containing nonelectrolytes of a given concentration by measuring the concentration
of the nonelectrolytes in a solution which contains electrolytes and the nonelectrolytes.
[0015] Still another object of the present invention is particularly to provide a measuring
method capable of directly and accurately measuring the concentration of a nonelectrolyte
in the agent A of a dialysate which contains electrolytes and the nonelectrolyte by
using a simple instrument, and in addition a preparation method and a preparation
apparatus capable of simply and accurately preparing a water solution of the agent
A containing a nonelectrolyte of a given concentration, by simply and accuratelty
measuring the concentration of the nonelectrolyte in the agent A using the above method.
[0016] In summary, the present invention is a method of measuring the concentration of a
nonelectrolyte in an electrolyte solution, comprising the steps of: measuring the
electric conductivity of the mixed electrolyte solution containing at least one electrolyte
and at least one nonelectrolyte; and determining the concentration of the nonelectrolyte
in the mixed solution from the measured electric conductivity based on the correlation
between the electric conductivity of the mixed solution and the concentration of the
nonelectrolyte determined previously as to the same system. In accordance with an
example of the present invention, the electrolyte is an electrolyte medicine mainly
composed of sodium chloride and the nonelectrolyte is a glucose medicine.
[0017] According to another aspect of the present invention, there is provided a method
of preparing a mixed solution, comprising the steps of: adding and mixing at least
one nonelectrolyte to and with an electrolyte solution while continuously measuring
the electric conductivity of the electrolyte solution; and determining the concentration
of the nonelectrolyte added to and mixed with the electrolyte solution from the measured
electric conductivity based on the correlation between the electric conductivity and
the concentration of the nonelectrolyte determined previously as to the same system,
to thereby obtain a mixed solution containing the electrolyte and the nonelectrolyte
with the nonelectrolyte set to a given concentration. In accordance with an example
of the present invention, the electrolyte solution is an electrolyte water solution
mainly composed of sodium chloride and the nonelectrolyte is glucose.
[0018] According to another aspect of the present invention, there is provided an apparatus
for preparing a mixed solution containing at least one electrolyte and at least one
nonelectrolyte, comprising: electrolyte storage means for storing the electrolyte;
nonelectrolyte storage means for storing the nonelectrolyte; water supply means for
supplying a predetermined amount of water; a preparation tank capable of accommodating
and stirring to uniformly mix a predetermined amount of the electrolyte supplied from
said electrolyte storage means, a predetermined amount of the nonelectrolyte supplied
from said nonelectrolyte storage means and a predetermined amount of the water supplied
from said water supply means; and an electric conductivity meter for measuring the
concentration of a water solution stirred and uniformly mixed in said preparation
tank; wherein after an electrolyte water solution of a given concentration is prepared
by supplying the electrolyte and the water into said preparation tank, a given amount
of the nonelectrolyte is supplied incrementally from said nonelectrolyte storage means
into said preparation tank to thereby prepare a mixed water solution, the concentration
of the nonelectrolyte in the mixed water solution is continuously measured by said
electric conductivity meter, and the supply of the nonelectrolyte from said nonelectrolyte
storage means into said preparation tank is stopped when the value of the concentration
reaches a given value. In accordance of an example of the present invention, said
apparatus is a preparation apparatus for the agent A of a dialysate, the electrolyte
is an electrolyte powder medicine mainly composed of a sodium chloride powder and
the nonelectrolyte is a glucose powder medicine.
[0019] According to still another aspect of the present invention, there is provided an
apparatus for preparing a mixed solution containing at least one electrolyte and at
least one nonelectrolyte, comprising: electrolyte storage means for storing the electrolyte;
nonelectrolyte storage means for storing the nonelectrolyte; water supply means for
supplying a given amount of water; a first preparation tank capable of accommodating
and stirring to uniformly mix a given amount of the electrolyte supplied from said
electrolyte storage means and a given amount of the water supplied from said water
supply means; a first electric conductivity meter for measuring the concentration
of an electrolyte water solution stirred and uniformly mixed in said first preparation
tank; a second preparation tank capable of accommodating and stirring to uniformly
mix the electrolyte water solution of a given concentration supplied from said first
preparation tank and a given amount of the nonelectrolyte supplied from said nonelectrolyte
storage means; and a second electric conductivity meter for measuring the concentration
of the nonelectrolyte in a mixed water solution stirred and uniformly mixed in said
second preparation tank; wherein a mixed water solution is prepared by incrementally
supplying a given amount of the nonelectrolyte from said nonelectrolyte storage means
into said second preparation tank, the concentration of the nonelectrolyte in the
mixed water solution is continuously measured by said second electric conductivity
meter, and the supply of the nonelectrolyte from said nonelectrolyte storage means
into said second preparation tank is stopped when the value of the concentration reaches
a given value. With an example of the present invention, said apparatus is a preparation
apparatus for the agent A of a dialysate, the electrolyte is an electrolyte powder
medicine mainly composed of a sodium chloride powder and the nonelectrolyte is a glucose
powder medicine. According to another example, the electrolyte contains at least first
and second electrolyte components and the electrolyte storage means comprises at least
first and second electrolyte storage means for separately storing the first and second
electrolyte components, respectively. In particular, said apparatus is a preparation
apparatus for the agent A of a dialysate, the electrolyte contains a first electrolyte
powder medicine composed of sodium chloride, a second electrolyte powder medicine
composed of sodium acetate and a third liquid electrolyte medicine composed of potassium
chloride and magnesium chloride as a small amount component, and the nonelectrolyte
is a glucose powder medicine.
BRIEF DESCRIPTION OF DRAWINGS
[0020]
Fig. 1 is a graph showing the change in electric conductivity when glucose is added
to a sodium chloride water solution;
Fig. 2 is a graph showing the correlation between the concentration of glucose and
the electric conductivity of a mixed water solution of sodium chloride and the glucose,
determined in Example 1;
Fig. 3 is a graph showing the change in electric conductivity when glucose is added
to a water solution of electrolytes excluding the glucose in the agent A of a dialysate;
Fig. 4 is a graph showing the correlation between the concentration of glucose and
the electric conductivity of a mixed water solution which contains electrolytes excluding
the glucose in the agent A of a dialysate and the glucose, determined in Example 2;
Fig. 5 is a graph showing the change in electric conductivity when saccharose is added
to a sodium chloride water solution;
Fig. 6 is a graph showing the correlation between the concentration of saccharose
and the electric conductivity of a mixed water solution of sodium chloride and the
saccharose, determined in Example 3;
Fig. 7 is a graph showing the change in electric conductivity when glucose is added
to a calcium chloride water solution;
Fig. 8 is a graph showing the correlation between the concentration of glucose and
the electric conductivity of a mixed water solution of calcium chloride and the glucose,
determined in Example 4;
Fig. 9 is a graph showing the change in electric conductivity when urea is added to
the water solution of the agent A (containing electrolytes and glucose) of a dialysate;
Fig. 10 is a graph showing the correlation between the concentration of urea and the
electric conductivity of a mixed water solution of the agent A of a dialysate and
the urea, determined in Example 5;
Fig. 11 is a graph showing the change in electric conductivity when albumin is added
to a water solution of electrolytes excluding the glucose of the agent A of a dialysate;
Fig. 12 is a graph showing the correlation between the concentration of albumin and
the electric conductivity of a mixed water solution which contains electrolytes excluding
the glucose of the agent A of a dialysate and the albumin, determined in Example 6;
Fig. 13 is a graph showing the change in electric conductivity when glucose is added
to a water solution of electrolytes excluding the glucose of the agent A of a dialysate;
Fig. 14 is a graph showing the correlation between the concentration of glucose and
the electric conductivity of a mixed water solution which contains electrolytes excluding
the glucose of the agent A of a dialysate and the glucose, determined in Example 7;
Fig. 15 is a view showing the schematic construction of an example of a preparation
apparatus for a mixed solution containing electrolytes and nonelectrolytes of the
present invention;
Fig. 16 is a view showing the schematic arrangement of another example of a preparation
apparatus for a mixed solution containing electrolytes and nonelectrolytes of the
present invention; and
Fig. 17 is a view showing the schematic arrangement of still another example of a
preparation apparatus for a mixed solution containing electrolytes and nonelectrolytes
of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0021] First, a method of measuring the concentration of a nonelectrolyte in an electrolyte
solution according to the present invention will be described.
[0022] A nonelectrolyte such as sugar, alcohol, amino acid is not dissociated to generate
ions even if it is dissolved in a polar solvent such as water. Thus, even if electrodes
of an electric conductivity meter are put into its solution and a voltage is imposed
thereto, no current flows. Therefore, until now it has been thought that not only
the concentration of a nonelectrolyte cannot be measured by the electric conductivity
meter but also that the correlation between the concentration of the nonelectrolyte
and the electric conductivity cannot be obtained.
[0023] In the preparation of the agent A of a dialysate, the inventors examined the change
of the electric conductivity of an intermediate concentration of electrolyte water
solution mainly composed of sodium chloride by sequentially adding and mixing glucose
as a nonelectrolyte to and with the electrolyte water solution and continuously measuring
the electric conductivity of the electrolyte water solution using the electric conductivity
meter. As a result, the inventors found that the detected electric conductivity changed
in accordance with the additive amount of the nonelectrolyte.
[0024] Further, as understood from the following examples, it was found that the above fact
also applied to a mixed solution containing electrolytes and nonelectrolytes other
than the dialysate and that when a nonelectrolyte was added to and mixed with an electrolyte
solution, the electric conductivity of the solution changed likewise.
Example 1
[0025] 6 gr of sodium chloride (electrolyte) was uniformly dissolved in one liter of water
at 20 °C to prepare a sodium chloride water solution having a concentration of about
3.7 mol/liter. One liter of the sodium chloride water was poured into a glass vessel
having a capacity of 1.5 liters and a pair of electrodes of an electric conductivity
meter (made by TOA Electronics Ltd., Commodity Name "CM-40S") were dipped into the
sodium chloride water solution.
[0026] Next, glucose powder was added to the sodium chloride water solution in the vessel
so that the concentration of the glucose was set to about 17.5 gr/liter in a mixed
water solution of the sodium chloride and the glucose, that is, about 17.5 gr glucose
was added to one liter of the sodium chloride water solution, and the glucose and
the water solution were stirred to be uniformly mixed together. On the other hand,
an AC voltage (voltage between peaks) Vp-p = about 30 mV was imposed between the pair
of electrodes of the electric conductivity meter and an electric current flowing between
the electrodes was detected to thereby measure the electric conductivity of the mixed
solution of the sodium chloride and the glucose. As shown in Fig. 1, although the
electric conductivity of the mixed water solution lowered at first as time elapsed
by the addition of the glucose, it took a constant value after a predetermined period
of time had elapsed.
[0027] Thereafter, another 17.5 gr of glucose were added two more times (that is, the concentration
of the glucose was set to about 35 gr/liter and about 52.5 gr/liter) and the electric
conductivity of the mixed water solution was measured. As shown in Fig. 1, although
the electric conductivity of the mixed water solution also lowered at first as time
elapsed, it had a constant value after a predetermined period of time had elapsed.
[0028] It is found from Fig. 1 that as the additive amount of the glucose increases, the
electric conductivity of the mixed water solution lowers. Fig. 2 shows the relationship
between the additive amount of the glucose, i.e. the concentration of the glucose
and the electric conductivity of the mixed water solution of the sodium chloride and
the glucose, wherein it is found that a fixed correlation, i.e. a linear correlation
exists between the concentration of the glucose and the electric conductivity.
Example 2
[0029] About 289 gr of an electrolyte substance which excludes the glucose in the agent
A of a dialysis solution was uniformly dissolved in one liter of water at 20 °C to
prepare a water solution (referred to as an agent A electrolyte concentration of 4.4
mol/liter). The above-mentioned electrolyte substance contains sodium chloride (NaCl),
potassium chloride (KCl), calcium chloride (CaCl
2·2H
2O), magnesium chloride (MgCl
2), and sodium acetate (CH
3COONa) in the ratio of NaCl : KCl : CaCl
2·2H
2O : MgCl
2·6H
2O : CH
3COONa = 1933 : 47 : 69 : 32 : 258. One liter of the water solution was poured into
a glass vessel with a capacity of 1.5 liters.
[0030] Next, glucose powder was added to the water solution in the vessel so that the concentration
of the glucose was set to about 74 mmol/liter in the mixed water solution of the electrolytes
and the glucose, that is, about 13.4 gr glucose was added to one liter of the electrolyte
water solution, and the glucose and the water solution were stirred to be uniformly
mixed. Then, the electric conductivity of the mixed water solution was measured using
the electric conductivity meter (made by TOA Electronics Ltd., Commodity Name "CM-40S")
as in Example 1. As shown in Fig. 3, although the electric conductivity of the mixed
water solution lowered at first as time elapsed, it had a constant value after a predetermined
period of time had elapsed.
[0031] Thereafter, amounts of about 13.4 gr of glucose were added incrementally (that is,
the concentration of the glucose was set to about 148, 188, 221.3 and 296 mmol/liter)
and the electric conductivity of the mixed water solution was measured. As shown in
Fig. 3, although the electric conductivity of the mixed water solution lowered at
first as time elapsed, it took a constant value after a predetermined period of time
had elapsed.
[0032] It is found from Fig. 3 that as the additive amount of the glucose increases, the
electric conductivity of the mixed water solution lowers. Fig. 4 shows the relationship
between the additive amount of the glucose, i.e. the concentration of the glucose
and the electric conductivity of the mixed water solution of the electrolytes and
the glucose, wherein it is found that a fixed correlation, i.e. a linear correlation
exists between the concentration of the glucose and the electric conductivity.
Example 3
[0033] About 205 gr of sodium chloride was uniformly dissolved in one liter of water at
20 °C to prepare a sodium chloride water solution having a concentration of about
3.5 mol/liter. One liter of the water solution was poured into a glass vessel having
a capacity of 1.5 liter.
[0034] Next, cane sugar powder (saccharose) was added to the water solution in the vessel
so that the concentration of the saccharose was set to about 19.5 mmol/liter in the
mixed water solution of the sodium chloride and the saccharose, that is, about 6.7
gr saccharose was added to one liter of the sodium chloride water solution, and the
saccharose and the water solution were stirred to be uniformly mixed together. Then,
the electric conductivity of the mixed water solution was measured using the electric
conductivity meter (made by TOA Electronics Ltd., Commodity Name "CM-40S") as in Example
1. As shown in Fig. 5, although the electric conductivity of the mixed water solution
lowered at first as time elapsed, it had a constant value after a predetermined period
of time had elapsed.
[0035] Thereafter, amounts of about 6.7 gr of saccharose were added incrementally (that
is, the concentration of the saccharose was set to about 39.0 mmol/liter and about
58.5 mmol/liter) and the electric conductivity of the mixed water solution was measured.
As shown in Fig. 5, although the electric conductivity of the mixed water solution
lowered at first as time elapsed, it had a constant value after a predetermined period
of time had elapsed.
[0036] It is found from Fig. 5 that as the additive amount of the saccharose increases,
the electric conductivity of the mixed water solution lowers. Fig. 6 shows the relationship
between the additive amount of the saccharose, i.e. the concentration of the saccharose
and the electric conductivity of the mixed water solution of the sodium chloride and
the saccharose, wherein it is found that a fixed correlation, i.e. a linear correlation
exists between the concentration of the saccharose and the electric conductivity.
Example 4
[0037] About 163 gr of sodium chloride (two molecules of water of crystallization) was uniformly
dissolved in one liter of water at 20 °C to prepare a sodium chloride water solution
having a concentration of about 1.11 mol/liter. One liter of the water solution was
poured into a glass vessel with a capacity of 1.5 liter.
[0038] Next, glucose powder was added to the water solution in the vessel so that the concentration
of the glucose was set to about 74 mmol/liter in the mixed water solution of the calcium
chloride and the glucose, that is, about 13.4 gr glucose was added to one liter of
the calcium chloride water solution and, the glucose and the water solution were stirred
to be uniformly mixed together. Then, the electric conductivity of the mixed water
solution was measured using the electric conductivity meter (made by TOA Electronics
Ltd., Commodity Name "CM-40S") as in Example 1. As shown in Fig. 7, although the electric
conductivity of the mixed water solution lowered at first as time elapsed, it had
a constant value after a predetermined period of time had elapsed.
[0039] Thereafter, amounts of about 13.4 g of glucose was added incrementally (that is,
the concentration of the glucose was set to about 148 mmol/liter and about 222 mmol/liter)
and the electric conductivity of the mixed water solution was measured. As shown in
Fig. 7, although the electric conductivitiy of the mixed water solution lowered at
first as time elapsed, it had a constant value after a predetermined period of time
had elapsed.
[0040] It is found from Fig. 7 that as the additive amount of the glucose increases, the
electric conductivity of the mixed water solution lowers. Fig. 8 shows the relationship
between the additive amount of the glucose, i.e. the concentration of the glucose
and the electric conductivity of the mixed water solution of the calcium chloride
and the glucose, wherein it is found that a fixed relative correlation, i.e. a linear
correlation exists between the concentration of the glucose and the conductivity.
Example 5
[0041] 303 gr of the agent A of a dialysate was uniformly dissolved in one liter of water
at 20 °C to prepare a water solution (referred to as an agent A concentration of 4.4
mol/liter). The above-mentioned agent A contains an electrolyte substance which is
similar to that of Example 2 and is comoposed of sodium chloride (NaCl), potassium
chloride (KCl), calcium chloride (CaCl
2·2H
2O), magnesium chloride (MgCl
2) and sodium acetate (CH
3COONa), and in addition glucose (C
6H
12O
6) in the ratio of NaCl : KCl : CaCl
2·2H
2O : MgCl
2·6H
2O : CH
3COONa : C
6H
12O
6 = 1933 : 47 : 69 : 32 : 258 : 315.
[0042] Next, urea was added to the water solution in the vessel so that the concentration
of the urea was set to about 100 mmol/liter in the mixed water solution of the electrolyte
and the urea, that is, about 6 gr urea was added to one liter of the electrolyte water
solution, and the albumin and the water solution were stirred to be uniformly mixed
together. Then, the electric conductivity of the mixed water solution was measured
using the electric conductivity meter (made by TOA Electronics Ltd., Commodity Name
"CM-40S") as in Example 1. As shown in Fig. 9, although the electric conductivity
of the mixed water solution lowered at first as time elapsed, it had a constant value
after a predetermined period of time had elapsed.
[0043] Thereafter, amounts of about 6 gr of urea were added incrementally (that is, the
concentration of the urea was set to about 200 mmol/liter and about 300 mmol/liter)
and the elctric conductivity of the mixed water solutions were measured. As shown
in Fig. 9, although the electric conductivity of the mixed water solution also lowered
at first as time elapsed, it had a constant value after a predetermined period of
time had elapsed.
[0044] It is found from Fig. 9 that as the additive amount of the urea increases, the electric
conductivity of the mixed water solution lowers. Fig. 10 shows the relationship between
the additive amount of the urea, i.e. the concentration of the urea and the electric
conductivity of the mixed water solution of the electrolyte and the urea, wherein
it is found that a fixed correlation, i.e. a linear correlation exists between the
concentration of the urea and the electric conductivity.
Example 6
[0045] About 144 gr of an electrolyte substance which excludes the glucose in the agent
A of a dialysis solution similar to that of Exmaple 2 was uniformly dissolved in one
liter of water at 20 °C to prepare a water solution (referred to as an agent A electrolyte
concentration of 2.2 mol/liter). The above-mentioned electrolyte substance contains
sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl
2·2H
2O), magnesium chloride (MgCl
2) and sodium acetate (CH
3COONa) in the ratio of NaCl : KCl : CaCl
2·2H
2O : MgCl
2·6H
2O : CH
3COONa =1933 : 47 : 69 : 32 : 258. One liter of the water solution was poured into
a glass vessel with a capacity of 1.5 liters.
[0046] Next, albumin (protein) was added to the water solution in the vessel so that the
concentration of the albumin was set to about 0.7 gr/deciliter in the mixed water
solution of the electrolytes and the albumin, that is, about 0.7 gr albumin was added,
and the albumin and the water solution were stirred to be uniformly mixed together.
Then, the electric conductivity of the mixed water solution was measured using the
electric conductivity meter (made by TOA Electronics Ltd., Commodity Name "CM-40S")
as in Example 1. As shown in Fig. 11, although the electric conductivity of the mixed
water solution lowered at first as a time elapsed, it had a constant value after a
predetermined period of time had elapsed.
[0047] Thereafter, amounts of about 0.7 gr of albumin were added incrementally (that is,
the concentration of the albumin was set to about 1.4 gr/deciliter and about 2.1 gr/deciliter)
and the electric conductivity of the mixed water solution was measured. As shown in
Fig. 11, although the electric conductivity of the mixed water solutions also lowered
at first as time elapsed, it had a constant value after a predetermined period of
time had elapsed.
[0048] It is found from Fig. 11 that as the additive amount of the albumin increases, the
electric conductivity of the mixed water solution lowers. Fig. 12 shows the relationship
between the additive amount of the albumin, i.e. the concentration of the albumin
and the electric conductivity of the mixed water solution of the electrolyte and the
albumin, wherein it is found that a fixed relative correlation, i.e. a linear correlation
exists between the concentration of the albumin and the electric conductivity.
Example 7
[0049] About 8.5 gr of an electrolyte substance which excludes the glucose in agent A of
a dialysis solution similar to that of Exmaple 2 was uniformly dissolved in one liter
of water at 20°C to prepare a water solution (referred to as an agent A electrolyte
concentration of 0.13 mol/liter). The above-mentioned electrolyte substance contains
sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl
2·2H
2O), magnesium chloride (MgCl
2) and sodium acetate (CH
3COONa) in the ratio of NaCl : KCl : CaCl
2·2H
2O : MgCl
2·6H
2O : CH
3COONa = 1933 : 47 : 69 : 32 : 258. One liter of the water solution was poured into
a glass vessel with a capacity of 1.5 liters.
[0050] Next, glucose powder was added to thewater solution in the vessel so that the concentration
of the glucose was set to about 74 mmol/liter in the mixed water solution of the electrolytes
and the glucose, that is, about 13.4 gr glucose was added to one liter of the electrolyte
water solution, and the powder glucose and the water solution were stirred to be uniformly
mixed together. Then, the electric conductivity of the mixed water solution was measured
using the electric conductivity meter (made by TOA Electronics Ltd., Commodity Name
"CM-40S") as in Example 1. As shown in Fig. 13, although the electric conductivity
of the mixed water solution lowered at first as time elapsed, it had a constant value
after a predetermined period of time had elapsed.
[0051] Thereafter, amounts of about 13.4 gr of glucose were added incrementally to the vessel
(that is, the concentration of the glucose was set to about 148.0 mmol/liter and about
222.0 mmol/liter) and the electric conductivity of the mixed water solution was measured.
As shown in Fig. 13, although the electric conductivity of the mixed water solution
lowered at first as time elapsed, it had a constant value after a predetermined period
of time had elapsed.
[0052] It is found from Fig. 13 that as the additive amount of the glucose increases, the
electric conductivity of the mixed water solution lowers. Fig. 14 shows the relationship
between the additive amount of the glucose, i.e. the concentration of the glucose
and the electric conductivity of the mixed water solution of the electrolytes and
the glucose, wherein it is found that a fixed correlation, i.e. a linear correlation
exists between the concentration of the glucose and the electric conductivity.
[0053] It can be understood from the above Examples 1-7 that there is the fixed linear correlation
between the concentration of a nonelectrolyte in a mixed solution containing at least
one electrolyte and the nonelectrolyte and the electric conductivity of said mixed
solution.
[0054] The inventors have found based on the aforesaid novel knowledge that the concentration
of a nonelectrolyte in a mixed solution containing at least one electrolyte and the
nonelectrolyte can be measured by detecting the electric conductivity of the mixed
solution. That is, according to the present invention, there is provided a measuring
method in which the correlation between the electric conductivity and the concentration
of a nonelectrolyte is determined as to the same mixed solution of electrolytes and
nonelectrolytes, next the electric conductivity of a mixed solution containing the
electrolytes and the nonelectrolytes whose concentration is unknown is measured and
then the concentration of the nonelectrolyte in the mixed solution is determined from
the thus obtained electric conductivity and the above correlation.
[0055] As described above, the method of measuring the concentration of a nonelectrolyte
according to the present invention can directly and accurately measure the concentration
of a nonelectrolyte such as sugar, protein, alcohol, amino acid or the like in a solution
which coexists with electrolytes, by using an electric conductivity meter which is
one of the most stable concentration detecting instruments having the least number
of variable factors.
[0056] Since the electric conductivity changes with the change of the temperature of a solution,
it is also required in the measuring method of the present invention that the measurement
is conducted at a given constant temperature, for example, at 20°C or at a temperature
near 20°C (for example, at 20°C ± 0.5 °C). The electric conductivity meter used in
the above respective examples (made by TOA Electronics Ltd., Commodity Name "CM-40S")
was an electric conductivity meter having an automatic temperature compensation function
which detects the temperature of the solution using a thermistor and sets a solution
temperature coefficient to thereby decrease the change of electric conductivity due
to the change in liquid temperature within a range corresponding to 0.5 °C.
[0057] Since the electric conductivity itself cannot be measured when the concentration
of electrolytes in a solution is too low, the concentration thereof must be sufficiently
high to enable the measurement of the electric conductivity. For example, as to the
measurement of the agent A of a dialysate, the concentration of the electrolytes in
the undiluted water agent A is usually 0.1 - 5.5 mol/liter and measuring this high
concentration is easily carried out by the method of the present invention.
[0058] Further, the method of measuring the concentration of a nonelectrolyte by electric
conductivity according to the present invention is also applicable to the preparation
of a mixed solution containing electrolytes and nonelectrolytes of a predetermined
concentration. That is, a nonelectrolyte is added to and mixed with an electrolyte
solution while continuously measuring the electric conductivity of the electrolyte
solution, and then the concentration of the nonelectrolyte added to and mixed with
the electrolyte solution is determined from the measured electric conductivity based
on the correlation between the electric conductivity and the concentration of the
nonelectrolyte determined previously as to the same system.
[0059] Therefore, when the electric conductivity detected by the electric conductivity meter
reaches a predetermined value, the addition of the nonelectrolyte are stopped, thereby
a mixed solution of the electrolytes and the nonelectrolytes having the target concentration
of the nonelectrolytes can be obtained.
[0060] Next, a preparation method of a mixed solution containing electrolytes and a nonelectrolyte
and an apparatus therefor will be described in detail.
Example 8
[0061] In the present example, likewise to the description of Example 1, with respect to
a mixed solution of sodium chloride as an electrolyte and glucose as a nonelectrolyte,
the correlation between the concentration of the glucose and the electric conductivity
shown in Fig. 2 was obtained by measuring the electric conductivity of the mixed solution
of the sodium chloride and the glucose, using the electric conductivity meter (CM-40S)
made by TOA Electronics Ltd. The concentration of the sodium chloride was fixed to3.7
mol/liter (constant) and the measurement was conducted while changing the concentration
of the glucose.
[0062] In the present example, a mixed water solution of an electrolyte (sodium chloride)
and a nonelectrolyte (glucose) was prepared so that the concentration of the glucose
was set to 35 gr/liter by adding and mixing glucose to and with the sodium chloride
water solution which had a constant concentration similar to the above 3.7 mol/liter
by the following operation.
[0063] That is, glucose powder was incrementally added to and mixed with a sodium chloride
water solution having the same concentration of 3.7 mol/liter as the above while continuously
measuring the electric conductivity of the water solution using the same electric
conductivity meter as the above. Although the electric conductivity of the water solution
containing only sodium chloride of the above concentration was 200 mS/cm, the measured
electric conductivity of the water solution lowered as the additive amount of glucose
increased.
[0064] According to the graph of Fig. 2 showing the predetermined correlation between the
concentration of the glucose and the electric conductivity, since the electric conductivity
at a target concentration of glucose of 35 gr/liter was 186 mS/cm, the addition of
the glucose was stopped when the measured electric conductivity reached the above
value (186 mS/cm).
[0065] The concentration of the glucose in the solution prepared in this example was measured
to be 35 gr/liter by a glucose analyzer (glucose oxidase method) (Model GLU-1 made
by TOA Electronics Ltd.). This measured concentration well coincided with the concentration
of theglucose determined from the electric conductivity according tothe present invention.
Further, the reproducibility of the concentration of glucose was about ± 1.4%.
Example 9
[0066] Fig. 15 shows the schematic arrangement of a preparation apparatus 1 for a dialysate,
in particular, for the agent A as an embodiment of a preparation apparatus of the
present invention.
[0067] The agent A preparation apparatus 1 includes a storage unit 11 such as a hopper storing
electrolyte powder medicine 101 containing electrolytes excluding glucose of the agent
A in a dialysate, that is, sodium chloride (NaCl), potassium chloride (KCl), calcium
chloride (CaCl
2·2H
2O), magnesium chloride (MgCl
2), and sodium acetate (CH
3COONa) in the ratio of NaCl : KCl : CaCl
2·2H
2O MgCl
2·6H
2O : CH
3COONa =1933 : 47 : 69 : 32 : 258, and a storage unit 12 such as a hopper storing glucose
powder 102 as a nonelectrolyte. The electrolyte medicine 101 and the nonelectrolyte
(glucose) medicine 102 are supplied from supply units 13 and 14 to a preparation tank
15, respectively. A pipe 16 is further connected to the preparation tank 15 and water
is supplied to the tank through the pipe 16. The amount of water to be supplied is
regulated by an electromagnetic valve 17. Although the water may be tap water not
containing bacterium, processed water such as R/O water (water processed by a reverse
osmosis membrane) or the like is preferably used. Further, it is preferable to provide
a warming device (not shown) with the preparation tank 15 to warm the tank 15 to about
25°C - 30 °C so as to shorten a dissolving time in the supplied R/O water in a colder
season.
[0068] The water, electrolyte medicine 101 and glucose medicine 102 supplied into the preparation
tank 15 are mixed with one another to prepare a mixed water solution (agent A).
[0069] A pump 19 is connected to the outlet of the preparation tank 15 through a pipe 18.
Connected to the pump 19 is a pipe 20 for returning the mixed water solution discharged
from the preparation tank 15 to the same again and a pipe 21 for supplying the mixed
water solution of a given concentration (agent A) prepared in the preparation tank
15 to a preparation /storage tank (not shown) or a dialysis apparatus (not shown)
directly so as to mix it together with the agent B of the dialysate (sodium hydrogencarbonate
water solution).
[0070] Electromagnetic valves 22 and 23 are disposed to the pipes 20 and 21, respectively,
and the pipe 20 or the pipe 21 can be selectively used by switching the electromagnetic
valves 22, 23.
[0071] An electric conductivity meter 24 is further disposed to the pipe 20 to measure the
concentration of the electrolytes or the nonelectrolyte of the mixed water solution
in the preparation tank 15. The aforesaid electric conductivity meter (made by TOA
Electronics Ltd., Model "CM-40S") can be preferably used as the electric conductivity
meter 24.
[0072] Next, operation of the preparation apparatus constructed as described above will
be described. First, the electromagnetic valve 17 is opened and R/O water is introduced
into the preparation tank 15 through the pipe 16. The amount of the water is measured
by a metering unit 25 such as a float switch disposed in the preparation tank 15.
When the amount of the water is measured, the pump 19 is operated with the valve 22
opened and the valve 23 closed. With this operation, the water in the preparation
tank 15 is circulated through the pipes 18 and 20. Subsequently, the electrolyte medicine
101 is supplied from the hopper 11 into the preparation tank 15 through the supply
unit 13. The electrolyte medicine 101 is stirred and mixed by the circulating water
in the preparation tank 15. Therefore, the electric conductivity meter 24 disposed
in the pipe 20 can measure the concentration of the electrolyte mixed water solution
flowing in the pipe 20. The electrolyte medicine 101 is supplied into the preparation
tank 15 as necessary in response to the indication of the electric conductivity meter
24 so as to prepare an electrolyte water solution mainly composed of sodium chloride
of a given concentration.
[0073] After the electrolyte water solution mainly composed of sodium chloride of the given
concentration is prepared in the preparation tank 15, each given amount of the glucose
powder medicine 102 is incrementally supplied from the hopper 12 into the preparation
tank 15 through the supply unit 14. The electrolyte water solution and the glucose
in the preparation tank 15 are sufficiently stirred by being circulated and flown
through the pipe 20 by the pump 19, so that a mixed water solution of the electrolytes
and the glucose is prepared. The concentration of the glucose in the mixed water solution
of the electrolytes and the glucose in the preparation tank 15 can be measured by
the electric conductivity meter 24 disposed in the pipe 20 when the water solution
flows through the pipe 20.
[0074] That is, as to the agent A of a dialysate as shown, for example, in Fig. 4, the correlation
between the electric conductivity of a mixed water solution and the concentration
of the glucose (nonelectrolyte) is determined when the glucose is added to an electrolyte
water solution mainly composed of sodium chloride of a predetermined concentration,
and next the electric conductivity of a mixed water solution containing the electrolytes
and the nonelectrolyte whose concentration is unknown is measured, then the concentration
of the glucose in the mixed solution can be measured from the thus obtained electric
conductivity and the above correlation.
[0075] When the mixed water solution containing the glucose of a predetermined concentration
is prepared in the preparation tank 15, the valve 22 is closed and the valve 23 is
opened so that the mixed water solution (agent A) set to the predetermined concentration
in the preparation tank 15 is supplied to the preparation/storage tank (not shown)
or the like while flowing through the pipe 21. An electrolyte solution (agent B) composed
of sodium hydrogencarbonate of a given concentration prepared by another apparatus
is supplied into the preparation/storage tank, so that a dialysate of a given concentration
or an undiluted dialysate is prepared.
Example 10
[0076] Fig. 16 shows another example of the preparation apparatus. Although the present
example is a preparation apparatus 1 for a dialysate and in particular for the agent
A of the dialysate as in Example 9, the present example is different from Example
9 in that preparation tanks 15 (15A, 15B) are provided for an electrolyte medicine
101 and a nonelectrolyte (glucose) medicine 102, respectively. Therefore, the members
of the present example whose functions are similar to those of the preparation apparatus
of Example 9 are denoted by the same numerals as used in Example 9 and a detailed
description thereof is omitted.
[0077] Operation of the preparation apparatus 1 of the present example will be described.
First, an electromagnetic valve 17 is opened and R/O water is introduced into the
preparation tank 15A through a pipe 16. The amount of water is metered by a float
switch 25A. When the desired amount of water is measured, a pump 19A is operated in
the state that a valve 22 is opened and a valve 31 is closed. With this operation,
the water in the preparation tank 15A is circulated through pipes 18A and 20A.
[0078] Subsequently, the electrolyte medicine 101 is supplied into the preparation tank
15A through a supply unit 13. The electrolyte medicine 101 is stirred and mixed by
the circulating water. Therefore, the electric conductivity meter 24A disposed in
the pipe 20A can measure the concentration of an electrolyte mixed water solution
flowing through the pipe 20A. An electrolyte water solution mainly composed of sodium
chloride of a given concentration is prepared by the electrolyte medicine 101 supplied
into the preparation tank 15A as necessary in response to the indication of the electric
conductivity meter 24A. When the electrolyte water solution mainly composed of the
sodium chloride of the given concentration is prepared in the preparation tank 15A,
the valve 31 and a valve 23 are opened, a valve 32 is closed and a pump 19B is operated.
With this operation, the electrolyte water solution set to a given concentration in
the preparation tank 15A is introduced into the preparation tank 15B. When it is detected
by a float switch 25B that the predetermined amount of the electrolyte water solution
has been introduced into the preparation tank 15B, the pump 19B is stopped and the
valve 31 is closed.
[0079] Next, predetermined amounts of the glucose powder medicine 102 are incrementally
supplied from a hopper 12 into the preparation tank 15B by a supply unit 14. The electrolyte
water solution and the glucose in the preparation tank 15B are sufficiently stirred
by being circulated by the pump 19B through a pipe 18C and a pipe 20B and made into
a mixed water solution of the electrolytes and the glucose. The concentration of the
glucose in the mixed water solution of the electrolytes and the glucose in the preparation
tank 15B is measured by an electric conductivity meter 24B disposed in the pipe 20B
by the same principle as that described in Example 9.
[0080] When the mixed water solution containing the glucose set to the given concentration
(agent A) is prepared in the preparation tank 15B as described above, the valve 32
is opened so that the mixed water solution set to the given concentration in the preparation
tank 15B is supplied to a preparation/storage tank (not shown) or the like by flowing
through the pipe 21. As above, an electrolyte solution composed of sodium hydrogencarbonate
of a predetermined concentration prepared by another apparatus (agent B) is supplied
to the preparation/storage tank so that a dialysate of a given concentration or an
undiluted dialysate is prepared.
[0081] It is contemplated in Example 9 described previously that in the case where the liquid
supplying process is executed after the dissolving process or a rinsing process is
executed prior to the dissolving process, a liquid remains in the pipes of the preparation
tank when a process is switched, for example, from the rinsing process to the dissolving
process. If the remaining liquid is mixed with a liquid having been dissolved, the
concentration of the mixed liquid is somewhat different from that of the liquid in
a dissolving tank. The construciton of Example 10 solves this problem.
[0082] It is needless to say that the problem can be solved in such an apparatus as Example
9 by obtaining the amount of liquid remaining when a process is switched, providing
a process which is operated prior to the start of the dissolving process and charging
glucose in the prior process.
Example 11
[0083] Fig. 17 shows still another example of the preparation apparatus. Although the present
example is a preparation apparatus 1 for a dialysate, in particular for an agent A
as in Example 10, the present example is different from Example 10 in that in the
preparation of an electrolyte medicine of a given concentration, a component to be
added in a small amount such as potassium chloride, magnesium chloride etc. is premixed
with a liquid agent, and in the preparation of an actual electrolyte water solution,
other powder medicines to be added in a large amount are dissolved and mixed with
the liquid agent in the preparation tank.
[0084] That is, in this example, potassium chloride, magnesium chloride etc. each of which
is a small amount-component among electrolyte medicines, is previously prepared as
a liquid agent 101C of a given concentration and filled in a vessel 11C and supplied
from the vessel 11C to a preparation tank 15A. Further, among the electrolyte medicines,
sodium chloride 101A is stored in a hopper 11A and sodium acetate 101B is stored in
a hopper 11b in a powder state, respectively. In the apparatus of the present example,
the members whose functions are similar to those of the preparation apparatus of Example
10 are denoted by the same numerals as used in Example 10 and the detailed description
thereof is omitted.
[0085] To describe operation of the preparation apparatus 1 of the present example, first,
an electromagnetic valve 17 is opened and R/O water is introduced into the preparation
tank 15A through a pipe 16. The amount of the water is measured by a float switch
25A. On the completion of the measuring of the water, a pump 19A is operated in the
state that a valve 22 is opened and a valve 31 is closed. With this operation, the
water in the preparation tank 15A is circulated through a pipe 18A and a pipe 20A.
[0086] Subsequently, the small-amount-component 101C in the vessel 11C is supplied into
the preparation tank 15A by a pump 33. The small-amount-component 101C is stirred
and mixed by circulating water. Therefore, a conductivity meter 24A disposed in the
pipe 20A can measure the concentration of the water solution of the small-amount-component
flowing through the pipe 20A. The small-amount-component 101C is supplied into the
preparation tank 15A as necessary in response to the indication of the conductivity
meter 24A to thereby prepare the water solution of the small amounts of the components
having a given concentration.
[0087] On the preparation of the water solution of the small-amount-component having the
given concentration in the preparation tank 15A, a valve 33 is closed and the sodium
chloride 101A among the electrolyte medicines is supplied from the hopper 11A into
the preparation tank 15A through a supply unit 13A. The sodium chloride 101A is stirred
and mixed by the circulating water solution of the small-amount-component. Therefore,
the electric conductivity meter 24A disposed in the pipe 20A can measure the concentration
of the electrolyte mixed water solution flowing through the pipe 20A. The sodium chloride
101A is supplied into the preparation tank 15A as necessary in response to the indication
of the electric conductivity meter 24A to thereby prepare a mixed water solution of
the small-amount-component and the sodium chloride having a given concentration.
[0088] Next, the sodium acetate 101B among the electrolyte medicines is supplied from a
hopper 11B into the preparation tank 15A through a supply unit 13B. The sodium acetate
101B is stirred and mixed by the circulating water solution of the small-amount-component
and the sodium chloride. Therefore, the electric conductivity meter 24A disposed in
the pipe 20A can measure the concentration of the electrolyte mixed water solution
flowing through the pipe 20A. The sodium acetate 101B is supplied into the preparation
tank 15A as necessary in response to the indication of the electric conductivity meter
24A to thereby prepare a mixed water solution of the small-amount-component, sodium
chloride and sodium acetate having a given concentration, that is, an electrolyte
water solution.
[0089] A method of mixing the thus prepared electrolyte water solution having a given concentration
with glucose after the preparation is the same as that of Example 10.
[0090] According to the present example, the apparatus can be reduced in size, and further,
an economical merit can be obtained because a medicine (agent A) whose components
are regulated to a predetermined mixing ratio is not necessary.
INDUSTRIAL APPLICABILITY
[0091] As described above, the method of measuring the concentration of a nonelectrolyte
in an electrolyte solution according to the present invention can accomplish the direct
and accurate measurement of the concentration of nonelectrolytes in a solution which
contains electrolytes and nonelectrolytes, by using a simple instrument. Further,
the preparation method and the preparation apparatus according to the present invention
can achieve the simple and accurate preparation of a mixed solution containing nonelectrolytes
of a given concentration by measuring the concentration of the nonelectrolytes in
a solution which contains electrolytes and nonelectrolytes.
[0092] In particular, according to the present invention, there is provided a measuring
method of directly and accurately measuring the concentration of the nonelectrolyte
in the agent A of a dialysate which contains electrolytes and the nonelectrolyte by
using a simple instrument, and in addition a preparation method and a preparation
apparatus capable of simply and accurately preparing a water solution of the agent
A containing a nonelectrolyte of a given concentration by measuring the concentration
of the nonelectrolyte in the agent A making use of the above measuring method.